Targeting HIF1α/miR-22/CDK8/KAT5 feedback loop inhibits hepatocellular carcinoma development
Journal Title: International Journal of engineering Research and Applications - Year 2017, Vol 7, Issue 8
Abstract
The glucose metabolism reprogramming is a hallmark of liver cancer. Although miR-22 has been reported to function as a tumor repressor in HCC, its role in aerobic glycolysis has not explicitly been explored. In this study, we supposed that miR-22 might be involved in the glucose metabolism reprogramming in hepatocellular carcinoma (HCC). We showed that knockdown of miR-22 caused a increase in generation of intracellular glucose and lactate, as well as a decrease in the oxygen consumption rate (OCR), which promotes metabolic switch from oxidative phosphorylation to aerobic glycolysis. Downregulation of miR-22-triggered glucose metabolism reprogramming promoted the growth of HCC in vivo. Mechanistically, miR-22 decreased the activity of hypoxia-inducible factor 1α (HIF1α) protein through directly targeting CDK8 and KAT5, forming a negative feedback loop of HIF1α/miR-22/CDK8/KAT5/HIF1α. Interestingly, we also indicated that HBx inhibited the miR-22 but elevated CDK8/KAT5 expression in HCC cells. Thus, these findings reveal a previously unappreciated function of miR-22 in HCC cell glycolysis and collectively highlight that miR-22 inhibits glucose metabolism reprogramming through suppressing CDK8/KAT5/HIF1α axis, which may be considered as one of the powerful effective therapeutics for HCC patients.
Authors and Affiliations
Wei Huang, Yanqiu Li, Xiaojing Jia, Chao Qu, Zhen Zhang, Ruixin He, Lizhe Wang, Fengming Ni, Donghe Su, He Huang, Yaqin Qu
Keywords
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